help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harrod, K. S.
Right arrow Articles by Jaramillo, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harrod, K. S.
Right arrow Articles by Jaramillo, R. J.

Am. J. Respir. Cell Mol. Biol., Volume 26, Number 2, February, 2002 216-223

Pseudomonas aeruginosa and Tumor Necrosis Factor-alpha Attenuate Clara Cell Secretory Protein Promoter Function

Kevin S. Harrod and Richard J. Jaramillo

Lovelace Respiratory Research Institute, Asthma and Pulmonary Immunology Program, Albuquerque, New Mexico

The Clara cell secretory protein (CCSP, also CC-10/uterglobin) is a 16-kD homodimeric protein abundantly expressed in the airways of mammals. Although the molecular function is unknown, gene-targeting studies indicate CCSP as a regulator of lung inflammation following acute respiratory infection or injury. CCSP is decreased in the lungs of mice following acute Pseudomonas aeruginosa (P.a.) infection. In the present study, the role of decreased promoter function in the regulation of CCSP by P.a. was assessed using an in vitro co-culture system and in vivo studies of transgenic mice. CCSP promoter activity in lung epithelial cells was markedly decreased by P.a. or tumor necrosis factor-alpha (TNF-alpha ) in a dose-dependent manner. Regulation of CCSP promoter function by either P.a. or TNF-alpha was localized to the proximal 166 bp flanking region of the CCSP promoter activity. Decreased regulation of the CCSP promoter by P.a. or TNF-alpha was specific to CCSP, as human surfactant protein D (SP-D) promoter activity was unaffected or increased by P.a. or TNF-alpha , respectively. A neutralizing antibody against human TNF-alpha was able to reverse both the TNF-alpha - mediated as well as P.a.-mediated decrease in CCSP promoter function in lung epithelial cells. TNF-alpha secretion by lung epithelial cells coincided with the decrease in CCSP promoter function following P.a. administration. Using a transgenic mouse model, P.a. administration to the lung markedly attenuated CCSP promoter-conferred gene expression in vivo. The attenuation of CCSP promoter activity in lung epithelial cells by P.a. involves, in part, autocrine/paracrine secretion of TNF-alpha , which in turn regulates CCSP transcription through cis-active elements in the proximal promoter region.

Abbreviations: aquaporin-5, AQP-5; beta -galactosidase, beta -Gal; Clara cell secretory protein, CCSP; CAATT-enhancer-binding protein, C/EBP; colony-forming units, cfu; cytomegalovirus, CMV; lipopolysaccharide, LPS; luciferase gene, luc; Pseudomonas aeruginosa, P.a.; reverse transcriptase- polymerase chain reaction, RT-PCR; reverse tetracycline transactivator, rtTa; surfactant protein, SP; tumor necrosis factor-alpha , TNF-alpha ; thyroid transcription factor-1, TTF-1.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. Livraghi, B. R. Grubb, E. J. Hudson, K. J. Wilkinson, J. K. Sheehan, M. A. Mall, W. K. O'Neal, R. C. Boucher, and S. H. Randell
Airway and Lung Pathology Due to Mucosal Surface Dehydration in {beta}-Epithelial Na+ Channel-Overexpressing Mice: Role of TNF-{alpha} and IL-4R{alpha} Signaling, Influence of Neonatal Development, and Limited Efficacy of Glucocorticoid Treatment
J. Immunol., April 1, 2009; 182(7): 4357 - 4367.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. L. Dinwiddie and K. S. Harrod
Human Metapneumovirus Inhibits IFN-{alpha} Signaling through Inhibition of STAT1 Phosphorylation
Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 661 - 670.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. S. Harrod, R. J. Jaramillo, C. L. Rosenberger, S.-Z. Wang, J. A. Berger, J. D. McDonald, and M. D. Reed
Increased Susceptibility to RSV Infection by Exposure to Inhaled Diesel Engine Emissions
Am. J. Respir. Cell Mol. Biol., April 1, 2003; 28(4): 451 - 463.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2002 American Thoracic Society. 		  CCM abstracts